Brachytherapy is an advanced form of interstitial radiation cancer treatment, in which radioactive seeds or sources are placed in or near the tumor itself, delivering a high radiation dose to the tumor while minimizing the radiation exposure in the surrounding healthy tissues. There have been numerous developments in brachytherapy. For example, U.S. Pat. No. 4,402,308 to Scott describes a technique wherein a hollow metal needle is inserted into the tumor and the seeds are thereafter inserted into the needle. As the needle is retracted from the tissue, the seeds are deposited in the tumor at desired locations. The instruments disclosed in the '308 patent to Scott are difficult to manipulate, given that their overall length is over 20 cm, and they are relatively heavy.
Another disadvantage of the technique disclosed by the above-referenced patent is that the seeds are deposited in a track made by the needle. Specifically, when the needle is withdrawn from the tissue, the seeds tend to migrate in the track, resulting in a poor distribution of seeds. Poor seed distribution can result in undesirable concentration(s) of seeds, causing either an over-dosage or an under-dosage of radiation. Additionally, over time, the seeds tend to migrate along the needle track away from the tumor; accordingly, patients commonly must repeat the procedure within a couple of months to have seeds re-implanted near the tumor.
Recently, integrated elongated assemblies, or “seed strands,” have been employed to introduce seeds into tumor sites. A pre-manufactured, elongated assembly or implant typically contains seeds that are spaced at 1 cm increments. The assembly is loaded into an introducer needle just prior to the implantation procedure.
There are many benefits to using seed strands in pre-implantation and post-implantation procedures. Seed strands are easier to handle and load into needles, since the strand structure eliminates the need to sort manually each seed and spacer. The “spacers” in the seed strands actually are integrated into the strand itself. Unlike loose seeds, which can migrate as the tumor grows or shrinks, a seed strand can maintain correct spacing between seeds even after being introduced into the body. The strands are sufficiently flexible and pliable to move with the tissue as the tissue shrinks back to pre-operative size. A seed strand also has sufficiently axial rigidity to allow easy expulsion of the strand from the implantation needle. In contrast, loose seeds have been known to jam inside an implantation needle.
A system for providing an elongated implant having radioactive seeds disposed therein is disclosed in U.S. Pat. No. 4,697,575 to Horowitz, which is incorporated herein by reference. In this system, a plurality of encapsulated radioactive seeds are positioned in a predetermined array. The seeds are encapsulated individually, with each capsule having a projection on one capsule end and a complementary recess on the remaining capsule end. A projection in one capsule is engageable with a recess in an adjacent capsule, such that the desired number of seeds can be plugged together to form a column of rigid, bio-absorbable and elongated material.
In another embodiment disclosed in the same patent, a rigid needle implant containing radioactive segments with break points is inserted into the tumor. The needle implant is made of a bio-absorbable polymer that is sufficiently rigid to be driven into the tumor without deflection and without use of a separate hollow needle. When the proper depth is reached with the rigid polymer needle, the remaining uninserted portion of the needle is broken off.
The above-referenced U.S. Patent Applications to Terwilliger and Lamoureux disclose additional seed strands, and are incorporated herein by reference. The seed strands comprise a bio-absorbable carrier material in the form of an elongated member with radioactive seeds disposed within the carrier material. The seeds are accurately spaced at a predetermined distance from one another, and maintain that spacing even after being introduced into the body. The elongated member is sufficiently axially rigid so as to maintain the spacing between seeds and to be easily injected into a tissue for treatment. The elongated member is also flexible and pliable enough to move with the tissue as the tissue shrinks back to pre-operative size. The devices can be used and placed with precision, and maintain their positions after the implantation, until the bio-compatible material dissolves and the seeds have become inert. The devices can be custom manufactured according to the pre-operative diagnosis for each patient, and as few as one patient's order can be manufactured at one time.
Before brachytherapy devices are shipped from the manufacturer, they must undergo rigorous sterilization. Sterilization methods include the use of steam sterilization, dry heat sterilization, radiation sterilization, gamma radiation, and chemical sterilization using agents such as hydrogen peroxide, chlorine dioxide, and ethylene oxide (“EtO”).
The use of EtO, a flammable, colorless gas at temperatures above 51.3° F. (10.7° C.), is one of the most commonly used sterilization methods. EtO is a potent anti-microbial agent that kills all known viruses, bacteria, and fungi, and is used to process sensitive instruments which cannot be adequately sterilized by other methods. Approximately half of the medical devices in the United States are sterilized with EtO.
The typical EtO sterilization process includes initial inventory control checks, placement of bio-indicators (“BI”), preconditioning, time inside the sterilization vessel, aeration, retrieval of the BIs, shipment of BIs to the testing laboratory, BI preparation, and as many as seven days of BI incubation. A test result report then must be compiled and communicated to the manufacturer. Only then can the manufacturers arrange return shipment of the tested lot to the manufacturing site for inspection and distribution.
Typical EtO sterilization times by a third-party certified facility are 2 days for processing and 7-10 days for the sterilization to be certified by bio-indicators that are incubated and tested. A given product lot could spend up to 11 days at a contract EtO facility, and even longer if weekends and holidays are taken into account. This turnaround time might be acceptable for most medical devices, and the price considered cost-effective for volume sterilization. However, for pre-packaged, radioactive delivery systems such as brachytherapy devices, time is of the essence. The period between the ordering of seeds to implanting them in the patient optimally should be as short as possible because the radioactivity of the seeds used in implants decays at a daily rate of about 3%, and because aggressive tumor growths should be treated with minimal delay.
To account for the additional time needed for sterilization, radioactive seeds used in interstitial radiation therapy are typically made “hotter” (i.e., more radioactive) than necessary when manufactured with the expectation that the seeds will have decayed to the proper activity level at the time of implantation. “Hotter” seeds are more expensive, and their use must be carefully monitored to ensure that the patient receives the precise dosage of radiation.
Further, since each implant can be custom-made according to each patient's pre-operative diagnosis and implantation may be required at any time, there is a need to economically sterilize as few as one patient's order as quickly as possible. Sterilization done at an outside facility would be cost-prohibitive because there is inadequate volume to spread the cost. Further, in most cases the devices cannot be sterilized along with other medical products because of differing pre-set sterilization requirements for the devices. The cost of sterilizing one patient's order would therefore bear the entire lot charge cost of a sterilization cycle.
It is possible to shorten the time and reduce the cost of sterilization by releasing sterilized devices based on “parametric release.” Parametric release is the release of sterilized products based on a declaration that the routine sterilization process performed is adequate, based solely on measurement and documentation of physical process parameters rather than the results of bio-indicators or product sterility evaluations. In other words, utilization of parametric release can avoid the costs and delays associated with incubating and testing with BIs.
EtO parametric release can be defined as a protocol that has been sufficiently tested to assure a kill rate of 10−6 Sterility Assurance Level (“SAL”), with an allowable EtO residual measurement after the sterilization cycle. Medical device manufacturers and sterilization contractors must validate the sterilization process in order to provide documented evidence that it will consistently yield the desired SAL. Upon completing all stages of validation, routine control procedures are established for subsequent cycles, which consist of monitoring the physical parameters of the process. The sterilized products may be released upon confirmation that the routine production cycle has fallen within the parameters established during validation. In other words, sterility testing on the actual finished products can be reduced or even eliminated.